Recent Developments on the Synthesis and Bioactivity of Ilamycins/Rufomycins and Cyclomarins, Marine Cyclopeptides That Demonstrate Anti-Malaria and Anti-Tuberculosis Activity.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractIlamycins/rufomycins and cyclomarins are marine cycloheptapeptides containing unusual amino acids. Produced by Streptomyces sp., these compounds show potent activity against a range of mycobacteria, including multidrug-resistant strains of Mycobacterium tuberculosis. The cyclomarins are also very potent inhibitors of Plasmodium falciparum. Biosynthetically the cyclopeptides are obtained via a heptamodular nonribosomal peptide synthetase (NRPS) that directly incorporates some of the nonproteinogenic amino acids. A wide range of derivatives can be obtained by fermentation, while bioengineering also allows the mutasynthesis of derivatives, especially cyclomarins. Other derivatives are accessible by semisynthesis or total syntheses, reported for both natural product classes. The anti-tuberculosis (anti-TB) activity results from the binding of the peptides to the N-terminal domain (NTD) of the bacterial protease-associated unfoldase ClpC1, causing cell death by the uncontrolled proteolytic activity of this enzyme. Diadenosine triphosphate hydrolase (PfAp3Aase) was found to be the active target of the cyclomarins in Plasmodia. SAR studies with natural and synthetic derivatives on ilamycins/rufomycins and cyclomarins indicate which parts of the molecules can be simplified or otherwise modified without losing activity for either target. This review examines all aspects of the research conducted in the syntheses of these interesting cyclopeptides.
CitationMar Drugs. 2021 Aug 3;19(8):446. doi: 10.3390/md19080446.
AffiliationHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
The following license files are associated with this item:
- Creative Commons
- Total synthesis of cyclomarins A, C and D, marine cyclic peptides with interesting anti-tuberculosis and anti-malaria activities.
- Authors: Barbie P, Kazmaier U
- Issue date: 2016 Jul 7
- Synthesis of New Cyclomarin Derivatives and Their Biological Evaluation towards Mycobacterium Tuberculosis and Plasmodium Falciparum.
- Authors: Kiefer A, Bader CD, Held J, Esser A, Rybniker J, Empting M, Müller R, Kazmaier U
- Issue date: 2019 Jul 2
- Rufomycins or Ilamycins: Naming Clarifications and Definitive Structural Assignments.
- Authors: Zhou B, Achanta PS, Shetye G, Chen SN, Lee H, Jin YY, Cheng J, Lee MJ, Suh JW, Cho S, Franzblau SG, Pauli GF, McAlpine JB
- Issue date: 2021 Oct 22
- Antimycobacterial Rufomycin Analogues from <i>Streptomyces atratus</i> Strain MJM3502.
- Authors: Zhou B, Shetye G, Yu Y, Santarsiero BD, Klein LL, Abad-Zapatero C, Wolf NM, Cheng J, Jin Y, Lee H, Suh JW, Lee H, Bisson J, McAlpine JB, Chen SN, Cho SH, Franzblau SG, Pauli GF
- Issue date: 2020 Mar 27
- Characterization of Regulatory and Transporter Genes in the Biosynthesis of Anti-Tuberculosis Ilamycins and Production in a Heterologous Host.
- Authors: He J, Wei X, Yang Z, Li Y, Ju J, Ma J
- Issue date: 2020 Apr 17